title: Age-related EBV-associated lymphoproliferative disorders in the Western population: a spectrum of reactive lymphoid hyperplasia and lymphoma.
abstract: We investigated age-related EBV(+) B-cell lymphoproliferations in the Western population. The clinical features, histology, immunophenotype, EBV-encoded RNA in situ hybridization, and clonality by PCR of T-cell receptor gamma and immunoglobulin genes were categorized in 122 EBV(+) lesions as follows: (1) reactive lymphoid hyperplasia; (2) polymorphic extranodal or (3) polymorphic nodal lymphoproliferative disease (LPD); and (4) diffuse large B-cell lymphoma (DLBCL). Interphase FISH for IG and PAX5 gene rearrangements was performed on 17 cases of DLBCL. The overall median age was 75 years (range, 45-101 years; 67 men, 55 women), and 67, 79, 73, and 77 years, respectively, for groups 1 through 4. Sixteen of 21 cases of polymorphic extranodal LPD were classified as EBV(+) mucocutaneous ulcer. PCR for immunoglobulin genes was polyclonal in reactive lymphoid hyperplasia (84%) and monoclonal in 33%, 63%, and 56% of polymorphic extranodal and nodal LPD cases and DLBCL, respectively. All groups showed restricted/clonal T-cell receptor responses (27%-70%). By FISH, 19% of DLBCLs showed IGH@ rearrangements, but PAX5 was unaffected. Disease-specific 5-year survival was 100%, 93%, 57%, and 25% for groups 1-4, respectively, and 100% for patients with EBV(+) mucocutaneous ulcer. Disease volume was predictive of therapy response (P = .0002), and pathologic subtype was predictive of overall outcome (P = .001). Age-related EBV(+) B-cell LPD encompasses a wider disease spectrum than previously recognized and includes both reactive and neoplastic conditions. Reduction in the T-cell repertoire may contribute to decreased immune surveillance.
authors.affiliation: Department of Pathology, University Hospital of Wales, Cardiff, UK.
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Dojcinov
authors.forename: Girish
authors.initials: G
authors.lastname: Venkataraman
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.forename: Iwona
authors.initials: I
authors.lastname: Wlodarska
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Schrager
authors.forename: Mark
authors.initials: M
authors.lastname: Raffeld
authors.forename: Robert K
authors.initials: RK
authors.lastname: Hills
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology; D019049:Developed Countries; D020031:Epstein-Barr Virus Infections / Q000209:etiology* / Q000473:pathology / Q000821:virology; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000209:etiology* / Q000473:pathology / Q000821:virology; D008232:Lymphoproliferative Disorders / Q000209:etiology* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019310:Pseudolymphoma / Q000209:etiology* / Q000473:pathology / Q000821:virology